The objective of this application is the continued investigation of ReI(CO)3 compounds as models for next generation Tc/Re radionuclide agents. With the discovery of specific peptide and protein interactions during our previous grant period, we are moving our attention to this chemistry for the next program period. We are interested in developing targeted ReI(CO)3 compounds via the direct interaction of the Re(CO)3(H2O)3+ ion with polypeptides and proteins, which represents a departure from the traditional bifunctional chelate agent (BFCA) approach. Specifically, we wish to 1) Investigate the interactions between the Re(CO)3(H2O)3+ ion and peptides, extending our work on histidine and including cysteine and methionine as well as pyridine imine coupled amino acids, 2) Screen a peptide library for strong ReI(CO)3 binders to assist with the design of his-tag sequences, 3) modify proteins with ReI(CO)3 through his-tags (rna15), replacement of tris-histidine zinc sites with ReI(CO)3 (insulin and carbonic anhydrase) and the engineering of a ReI(CO)3 binding site (azurin). This work will be carried out primarily in the laboratories of Prof. Christopher J. Ziegler at the University of Akron, but significant assistance will come from Prof. Richard Herrick at the College of the Holy Cross. This project will support the training of two Ph.D. graduate students during the program period as well as two undergraduate researchers per year. Funds from the proposal will also be used to support the PI (one month per year) during the summers of the program period. The graduate students will be specialized in biochemical and inorganic methods; the undergraduate students will be trained in these areas by the graduate students. PUBLIC HEALTH RELEVANCE: This work is relevant to public health in several ways. First, this research will directly contribute to the development of new technetium radiopharmaceuticals that target specific tissues. Technetium-based imaging agents are the most common radionuclides in use in the clinic today, and are crucial for the imaging of brain, cardiovascular and skeletal structures. In addition, this grant will assist in the training of both graduate and undergraduate students who will go on to work in health related professions.